Leishmanicidal, antiplasmodial, and cytotoxic activity of novel diterpenoid 1,2-quinones from Perovskia abrotanoides: new source of tanshinones

TY - JOUR

T1 - Leishmanicidal, antiplasmodial, and cytotoxic activity of novel diterpenoid 1,2-quinones from Perovskia abrotanoides: new source of tanshinones

AU - Sairafianpour, M

AU - Christensen, J

AU - Staerk, D

AU - Budnik, B A

AU - Kharazmi, A

AU - Bagherzadeh, K

AU - Jaroszewski, J W

N1 - Keywords: Animals; Anti-Infective Agents; Antineoplastic Agents, Phytogenic; Antiprotozoal Agents; Chromatography, Thin Layer; Diterpenes; Drug Resistance; Humans; Iran; Lamiaceae; Leishmania major; Lymphocytes; Nuclear Magnetic Resonance, Biomolecular; Phenanthrenes; Phytohemagglutinins; Plant Lectins; Plant Roots; Plants, Medicinal; Plasmodium falciparum; Spectrometry, Mass, Matrix-Assisted Laser Desorption-Ionization; Tumor Cells, Cultured

PY - 2001

Y1 - 2001

N2 - Cryptotanshinone (1), a quinoid diterpene with a nor-abietane skeleton, and three new natural products, 1beta-hydroxycryptotanshinone (2), 1-oxocryptotanshinone (3), and 1-oxomiltirone (4), were isolated from roots of the Iranian medicinal plant Perovskia abrotanoides. Their structures were established using homo- and heteronuclear two-dimensional NMR experiments, supported by HRMS. The total amount of tanshinones isolated from dry roots of Perovskia abrotanoides was about 1.5%. The compounds exhibited leishmanicidal activity in vitro (IC(50) values in the range 18-47 microM). These findings provide a rationale for traditional use of the roots in Iran as a constituent of poultices for treatment of cutaneous leishmaniasis. The isolated tanshinones also inhibited growth of cultured malaria parasites (3D7 strain of Plasmodium falciparum), drug-sensitive KB-3-1 human carcinoma cell line, multidrug-resistant KB-V1 cell line, and human lymphocytes activated with phytohaemagglutinin A (IC(50) values in the range 5-45 microM). The toxicity of tanshinones toward the drug-sensitive KB-3-1 and the multidrug-resistant KB-V1 cells was the same, indicating that the compounds are not substrates for the P-glycoprotein drug efflux pump.

AB - Cryptotanshinone (1), a quinoid diterpene with a nor-abietane skeleton, and three new natural products, 1beta-hydroxycryptotanshinone (2), 1-oxocryptotanshinone (3), and 1-oxomiltirone (4), were isolated from roots of the Iranian medicinal plant Perovskia abrotanoides. Their structures were established using homo- and heteronuclear two-dimensional NMR experiments, supported by HRMS. The total amount of tanshinones isolated from dry roots of Perovskia abrotanoides was about 1.5%. The compounds exhibited leishmanicidal activity in vitro (IC(50) values in the range 18-47 microM). These findings provide a rationale for traditional use of the roots in Iran as a constituent of poultices for treatment of cutaneous leishmaniasis. The isolated tanshinones also inhibited growth of cultured malaria parasites (3D7 strain of Plasmodium falciparum), drug-sensitive KB-3-1 human carcinoma cell line, multidrug-resistant KB-V1 cell line, and human lymphocytes activated with phytohaemagglutinin A (IC(50) values in the range 5-45 microM). The toxicity of tanshinones toward the drug-sensitive KB-3-1 and the multidrug-resistant KB-V1 cells was the same, indicating that the compounds are not substrates for the P-glycoprotein drug efflux pump.

U2 - 10.1021/np010032f

DO - 10.1021/np010032f

M3 - Journal article

C2 - 11720520

SN - 0163-3864

VL - 64

SP - 1398

EP - 1403

JO - Journal of Natural Products

JF - Journal of Natural Products

IS - 11

ER -